9 research outputs found

    Pan-cancer analysis of whole genomes

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    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

    Drivers of variability in water use of native and non-native urban trees in the greater Los Angeles area

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    Trees in urban ecosystems are valued for shade and cooling effects, reduction of CO2 emissions and pollution, and aesthetics. However, in arid and semi-arid regions, urban trees must be maintained through supplemental irrigation, in competition with other water needs. Currently, a comprehensive understanding of the factors which influence water use of urban tree species is lacking. In order to study the drivers of whole tree water use of two common species in the Los Angeles Basin urban forest, four sites in Los Angeles and Orange County were instrumented with sap flow and meteorological sensors. These sites allowed comparisons of the water use of a native riparian (Platanus racemosa Nutt.; California sycamore) and non-native (Pinus canariensis C. Sm.; Canary Island pine) Mediterranean species, as well as the spatial variability in water use under different environmental and management conditions. We found higher rates of sapflux (J O ) in native California sycamore as compared to non-native Canary Island pine. Within each species, we found considerable site-to-site variability in the magnitude and seasonality of J O . For Canary Island pine, the majority of inter-site variability derived from differences in water availability: response to vapor pressure deficit was similar during a period without water limitations. In contrast, California sycamore did not appear to experience water limitation at any site; however, there was considerable spatial variability in water use, potentially linked to differences in nutrient availability. Whole tree transpiration (E) was similar for the two species when water was not limiting, but Canary Island pine was able to withstand unirrigated conditions with a very low E. These results add to the currently small pool of data on urban tree water use and ecophysiology, and contribute to establishing a more quantitative understanding of urban tree function
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